The purpose of these studies will be to investigate the regulation of apoprotein-B metabolism in human subjects. Apoprotein-B is a major component of very low density lipoprotein (VLDL) as the latter is secreted by the liver, remains intact as triglyceride is removed from VLDL in the plasma by the action of lipoprotein lipase, and finally is essentially the only protein in low density lipoprotein (LDL), as it leaves the vascular space with cholesterol. Because of its unique position as the carrier protein common to both VLDL and LDL, determination of the regulatory mechanisms governing the synthesis and degradation of apoprotein-B seems crucial to the understanding of the control of plasma lipoprotein concentrations. As an initial step toward such a goal, we have chosen to study the relationship of VLDL triglyceride secretion to VLDL apoprotein-B synthesis and degradation. In the present studies we will use radioactively labelled glycerol, autologous VLDL and autologous LDL to simultaneously determine the synthetic and fractional removal rates of VLDL triclyceride, VLDL apo-B, and LDL apo-B. In addition, the percent conversion of VLDL apo-B to LDL apo-B can be calculated from the data generated by such studies. These investigations will be carried out in normal subjects and subjects with elevated plasma VLDL triglyceride and/or LDL cholesterol levels. All subjects will be studied under identical baseline conditions and then entered into one of several studies designed to perturb VLDL triglyceride synthesis. This experimental design will enable us to complete large numbers of studies under identical control conditions and also generate a significant quantity of data concerned with the role of VLDL triglyceride synthesis in the regulation of apoprotein-B metabolism under differing conditions.